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Effect of androgens on Sertoli cell maturation in human testis from birth to puberty.

ABSTRACT: BACKGROUND:Androgens are well known to be necessary for spermatogenesis. The purpose of this study was to determine Sertoli cell responsiveness to androgens according to age from birth to puberty. RESULTS:Testicular tissue samples were studied in a population of 84 control boys classified into seven groups according to age: group 1 (1-30 days), group 2 (1-3 months), group 3 (3-6 months), group 4 (0.5-3 years), group 5 (3-6 years), group 6 (6-12 years), and group 7 (12-16 years). We compared these data with those of 2 situations of pathology linked to androgens: 1/premature secretion of testosterone: 4 cases of Leydig cell tumor (LCT) in childhood; and 2 /defect of androgen receptors (AR): 4 cases of complete form of insensitivity to androgen syndrome (CAIS). In control boys, AR immunoreactivity (ir) in Sertoli cells appeared between 4.6 and 10.8 years of age, Anti-Mullerian Hormone (AMH) ir in Sertoli cells disappeared between 9.2 and 10.2 years of age. Connexin 43 (Cx43) ir in Sertoli cells and histological features of the onset of spermatogenesis appeared between 10.8 and 13,8 years of age. Cx43 ir was significantly higher in 12-16 year-olds than in younger boys. In case of CAIS, no spermatogenesis was observed, both AR and Cx43 ir were undetectable and AMH ir was elevated in Sertoli cells even at pubertal age. In the vicinity of LCTs, spermatogenesis occurred and both AR and Cx43 ir were strongly positive and AMH ir in Sertoli cells was low for age. CONCLUSIONS:Androgen action on Sertoli cells is required for onset of spermatogenesis and premature androgen secretion by LCT can induce spermatogenesis in the vicinity of the tumor. AR ir appeared earlier than onset of spermatogenesis, with large interindividual variability. The timing and mechanisms of Sertoli cell responsiveness to androgens are important issues for understanding the induction of spermatogenesis at puberty.

SUBMITTER: Lapoirie M

PROVIDER: S-EPMC8670046 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSertoli cell-only syndrome (SCOS) is the most serious pathological type of non-obstructive azoospermia. Recently, several genes related to SCOS have been identified, including FANCM, TEX14, NR5A1, NANOS2, PLK4, WNK3, and FANCA, but they cannot fully explain the pathogenesis of SCOS. This study attempted to explain spermatogenesis dysfunction in SCOS through testicular tissue RNA sequencing and to provide new targets for SCOS diagnosis and therapy.MethodsWe analyzed differentially expressed genes (DEGs) based on RNA sequencing of nine patients with SCOS and three patients with obstructive azoospermia and normal spermatogenesis. We further explored the identified genes using ELISA and immunohistochemistry.ResultsIn total, 9406 DEGs were expressed (Log2|FC|≥ 1; adjusted P value < 0.05) in SCOS samples, and 21 hub genes were identified. Three upregulated core genes were found, including CASP4, CASP1, and PLA2G4A. Thus, we hypothesized that testis cell pyroptosis mediated by CASP1 and CASP4 might be involved in SCOS occurrence and development. ELISA verified that CASP1 and CASP4 activities in the testes of patients with SCOS were significantly higher than those in patients with normal spermatogenesis. Immunohistochemical results showed that CASP1 and CASP4 in the normal spermatogenesis group were mainly expressed in the nuclei of spermatogenic, Sertoli, and interstitial cells. CASP1 and CASP4 in the SCOS group were mainly expressed in the nuclei of Sertoli and interstitial cells because of the loss of spermatogonia and spermatocytes. CASP1 and CASP4 expression levels in the testes of patients with SCOS were significantly higher than those in patients with normal spermatogenisis. Furthermore, the pyroptosis-related proteins GSDMD and GSDME in the testes of patients with SCOS were also significantly higher than those in control patients. ELISA also showed that inflammatory factors (IL-1 β, IL-18, LDH, and ROS) were significantly increased in the SCOS group.ConclusionsFor the first time, we found that cell pyroptosis-related genes and key markers were significantly increased in the testes of patients with SCOS. We also observed many inflammatory and oxidative stress reactions in SCOS. Thus, we propose that testis cell pyroptosis mediated by CASP1 and CASP4 could participate in SCOS occurrence and development.

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Effect of androgens on Sertoli cell maturation in human testis from birth to puberty.

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